Endo-Q
Can the composition of an infant’s gut microbiome indicate the risk of one day developing type 1 diabetes?
Answer: Yes, but with caution. A study of babies in Sweden that analyzed stool samples collected when the children were approximately 1 year old indicates that certain microbial biomarkers are associated with increased risk of type 1 diabetes — up to 20 years before diagnosis.
Infant Gut Microbiome Association with Future Type 1 Diabetes
Discussion and Context
Over the next two decades, the global incidence of type 1 diabetes is expected to double1 from 8.4 million people to 17.4 million by 2040; yet a cure remains elusive. A lack of diversity or diminishment of healthy bacteria in the microbiome has been an area of inquiry into factors that lead to the development of the disease. Changes in the microbiome have been found to precede the occurrence of diabetes-associated autoantibodies,2 traditional markers for the disease. New research3 has identified gut microbial biomarkers in infants that are associated with future diagnoses of type 1 diabetes, providing opportunities for intervention long before clinical diagnosis typically would occur.
Researchers analyzed stool samples from 284 infants enrolled in a longitudinal general population cohort All Babies In Southeast Sweden (ABIS). At approximately 1 year old (12.5 months average), stool samples from healthy controls and those who developed type 1 diabetes were analyzed for 16S ribosomal RNA (rRNA) sequencing and quantitative polymerase chain reaction (PCR). The study measured microbial differences at taxonomic and core microbiome levels and used PICRUSt to predict functional makeup of segments of 16S rRNA.3
Results
Researchers reported 16 infants had a future diagnosis of type 1 diabetes at an average age of 13-plus years old. They analyzed 100 iterations of 32 matched control infants who did not develop the disease up to 20 years of age.3
Healthy control infants had a higher abundance of Parasutterella and Eubacterium, while Porphyromonas was more abundant in infants who were later diagnosed with type 1 diabetes. Additionally, Ruminococcus was significant in the differences in microbiome composition of control infants and those with future type 1 diabetes. In control infants, Flavonifractor and UBA1819 were the strongest differentiating factors and were found in higher abundance when compared to the babies who developed type 1 diabetes. The strongest factors for incidence of type 1 diabetes were Alistipes and Fusicatenibacter.3
Practical Takeaways
Researchers reported that differences in the taxonomy and function of the microbial makeup helped identify who would develop type 1 diabetes. They noted the possibility of disease prevention by altering diet or promoting a “healthy” gut microbiome early in life.
Further Insights
Lead author Malin Bélteky, MD of the department of biomedical and clinical sciences, division of children’s and women’s health, Linköping University, Sweden, explained the findings.
Based on these findings, is it possible that stool sampling for microbiota at an early age could help in early diagnoses of other autoimmune diseases, such as celiac or lupus?
Dr. Bélteky: The hypothesized link between microbiome composition differences and autoimmunity in type 1 diabetes, with certain bacterial metabolites promoting a proinflammatory gut environment leading to impaired epithelial barrier function and a faulty immune activation, could be transferred to other autoimmune disorders as well. More research into specific autoimmune disorders is necessary, and ongoing, but it is possible that similar differences could be observed in these patient groups as well.
As the cohort was limited to babies in Sweden, do you believe there was enough ethnic diversity among participants to infer that similar findings might occur in a more heterogenous population, for example, in the US?
Dr. Bélteky: The general population cohort ABIS, where these samples were collected, is a good representation of the Swedish population 1997 to 1999, which at that time was more homogenous in terms of ethnicity compared to the US. However, the healthy controls were carefully matched based on the HLA haplotypes associated with risk of developing T1D, which has been proven to affect the microbiome composition itself [Russel et al4]. It should be possible to find differences in microbiome composition with a careful control selection also in less homogenous populations.
What type of research is needed to follow up on your findings and move toward patient interventions?
The first year of life is associated with major changes in the gut microbiome composition as the infant is exposed to different environments and dietary changes from primarily breast milk or formula to solid food. At 12 months of age, around the time when the samples in this study were collected, the microbiome is rapidly maturing. A follow-up study with more frequent stool sampling around this age would be interesting, as well as studying changes in the microbiome in the time period immediately preceding autoantibody conversion in a general population. Interventional studies involving the gut microbiome are unfortunately likely far off in the future as this is still a developing area of research.
